This invention was made in the course of work supported by governmental financing, and the government therefore has certain rights in the invention. Specifically, the work was supported by N.I.H. grant CA 31798.
This invention relates to T-lymphocyte responses.
Antigen-specific T-lymphocyte-mediated killing is a multistep process involving antigen recognition by a cytolytic T lymphocyte (CTL), adhesion of the CTL to a target cell, delivery of a lethal hit, and target cell lysis. Bystander cells and the CTL itself are unharmed in the killing reaction, and the CTL can detatch and engage in further killing encounters. The response of Helper T lymphocytes to antigen, which is critical for the initiation of the immune response to many agents, is also dependent on adhesion of T lymphocytes to antigen presenting cells. Helper T lymphocyte responses are assayed by proliferation of lymphocytes or 1L-2 production.
The molecular basis of CTL-mediated killing and Helper T lymphocyte responses has been studied by preparing monoclonal antibodies (MAb) to both CTLs and their targets and selecting for those which block the killing response. Monoclonal antibodies to LFA-1 (LFA stands for lymphocyte function associated), CD2 (also called LFA-2, T11, or E-rosette receptor), and LFA-3 antigen molecules inhibit killing (Sanchez-Madrid et al., 79 Proc. Nat. Acad. Sci. 7489, 1982) and also inhibit Helper T lymphocyte dependent responses.
Human LFA-3 is a cell surface glycoprotein expressed on almost all human cells, which has a mean molecular weight of about 60,000 (Id.). It is immunoprecipitated by specific MAbs. LFA-3 is a found on target cells and antigen presenting cells, and killing of a target cell by an effector CTL or recognition of antigen presenting cells by Helper T lymphocytes is blocked by binding of LFA-3 MAb to the target cell or antigen presenting cells. Specifically, LFA-3 is found on monocytes, granulocytes, CTL's, B-lymphoblastoid cell lines, platelets, thymic epithelial cells, vascular endothelial cells, smooth muscle and fibroblasts (Krensky et al., Human cytolytic T-lymphocyte clones and their function-associated cell surface molecules, In Hybridoma technology in the biosciences and medicine, eds. Springer et al., Plenum Press, New York, 1985.